title: Absence of effect of SLC22A2 genotype on cisplatin-induced nephrotoxicity in oesophageal cancer patients receiving cisplatin and 5-fluorouracil: report of results discordant with those of earlier studies.
abstract: OBJECTIVE
  Cancer patients treated with cisplatin chemotherapy frequently experience drug-induced nephrotoxicity. Clinical studies using a single chemotherapeutic regimen or large sample sizes for patients with the SLC22A2 808T allele have not been reported. Here, we examined 95 patients with oesophageal cancer who received 5-fluorouracil and cisplatin (FP) to determine whether nephrotoxicity was affected by SLC22A2 808G>T polymorphism.
  
  
  METHODS
  The change rate of the estimated glomerular filtration rate (eGFR) was used for the evaluation of cisplatin-induced nephrotoxicity and calculated for each patient according to the following formula: change rate = (prechemotherapy value - post-chemotherapy value)/prechemotherapy value. Genotyping of SLC22A2 808G>T was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
  
  
  RESULTS
  The eGFR after FP chemotherapy was significantly lower than that before chemotherapy, and the mean difference in eGFR was 25·7 mL/min (P < 0·01). There was no significant difference in the mean change rate of the eGFR following FP chemotherapy between the SLC22A2 808GG genotype (n = 70) and the 808GT+TT genotypes (n = 25) (27·9% and 27·8%, respectively). In multiple regression analyses, the change rate of eGFR following FP chemotherapy was associated with the eGFR value prior to chemotherapy (P = 0·04).
  
  
  CONCLUSIONS
  In FP chemotherapy for oesophageal cancers, cisplatin-induced nephrotoxicity seems to be unaffected by the SLC22A2 808G>T polymorphism. The eGFR prior to chemotherapy might be an important risk factor for cisplatin-induced nephrotoxicity. Our present study was estimated with a single chemotherapeutic regimen, eGFR, and was calculated using serum creatinine, age and the sex of the patient and sample sizes of 25 patients with SLC22A2 808T allele. However, further examinations with a larger sample size to corroborate the study results might be necessary.
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hinai
authors.forename: S
authors.initials: S
authors.lastname: Motoyama
authors.forename: T
authors.initials: T
authors.lastname: Niioka
authors.forename: M
authors.initials: M
authors.lastname: Miura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001772:Blood Cell Count; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004247:DNA / Q000235:genetics; D004573:Electrolytes / Q000097:blood; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D012044:Regression Analysis
chemical_list: D000970:Antineoplastic Agents; D004573:Electrolytes; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D004247:DNA; D002945:Cisplatin; D005472:Fluorouracil
keywords: SLC22A2; cancer; cisplatin; nephrotoxicity